Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study—protocol for a phase 3, randomized, controlled trial

Background Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. Methods ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. Discussion RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-023-07831-x.


SPIRIT Checklist for Trials
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Upload your completed checklist as an additional file when you submit to Trials.You must reference this additional file in the main text of your protocol submission.The completed SPIRIT figure must be included within the main body of the protocol text and can be downloaded here: http://www.spiritstatement.org/schedule-of-enrolment-interventions-and-assessments/In your methods section, please state that you used the SPIRIT reporting guidelines, and cite them as: Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin J, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D.
SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials.BMJ. 2013;346

(protocol deviations)]
There are no plans to promote participant

Methods: Monitoring
Data monitoring: formal committee #21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol.
Alternatively, an explanation of why a DMC is not It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items.
Amendments to the protocol should be tracked and dated.The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons "Attribution-NonCommercial-NoDerivs 3.0 Unported" license.This checklist can be completed online using https://www.goodreports.org/,a tool made by the EQUATOR Network in collaboration with Penelope.ai of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification.To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants will be blinded after assignment to interventions (eg, trial participants, care Pages 13, lines 353-359] providers, outcome assessors, data analysts)for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known.Reference to where data collection forms can be found, of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation n/a] Patients will receive routine post-trial care as prescribed by their physicians; the Sponsor will not provide ancillary or posttrial care.Risks associated with participation in this trial are deemed to be minimal; no compensation for subjects who suffer harm is planned.]for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable n/a] The current protocol does not include plans for genetic or molecular analyses on biological specimens.Additional consent will be sought from patients should any ancillary studies be planned with archived specimens (Page 9, lines232-234).